Document Detail


DNA methylation is not likely to be responsible for aggrecan down regulation in aged or osteoarthritic cartilage.
MedLine Citation:
PMID:  15708898     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: Expression of aggrecan is reduced during aging and osteoarthritic cartilage degeneration. CpG methylation may have a role in the down regulation of aggrecan transcriptions. OBJECTIVE: To investigate whether a correlation between gene methylation and expression of aggrecan in chondrocytes exists. METHODS: The human aggrecan promoter region was analysed computationally for CpG-rich regions. These were investigated for the methylation of C residues in normal (aged) and osteoarthritic chondrocytes by the bisulphite method for modifying DNA as well as sequence analysis using DNA directly extracted from normal and osteoarthritic cartilage tissue. Additionally, chondrocytic cell lines were investigated for methylation within the aggrecan promoter region. RESULTS: The CpG-rich promoter region of the human aggrecan gene contains a 0.6 kb region that meets the criteria of a CpG island as defined by prediction programmes. A significant correlation of aggrecan mRNA expression levels and methylation status in normal (aged) and osteoarthritic chondrocytes as well as in different chondrocytic cell lines was not found. CONCLUSIONS: Expression of aggrecan in normal cartilage and diseased states is not modulated by gross changes of CpG methylation of its promoter region. CpG methylation does not have a central role in the switch off of aggrecan promoter activity in human adult articular chondrocytes.
Authors:
E Pöschl; A Fidler; B Schmidt; A Kallipolitou; E Schmid; T Aigner
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Annals of the rheumatic diseases     Volume:  64     ISSN:  0003-4967     ISO Abbreviation:  Ann. Rheum. Dis.     Publication Date:  2005 Mar 
Date Detail:
Created Date:  2005-02-14     Completed Date:  2005-03-07     Revised Date:  2008-11-21    
Medline Journal Info:
Nlm Unique ID:  0372355     Medline TA:  Ann Rheum Dis     Country:  England    
Other Details:
Languages:  eng     Pagination:  477-80     Citation Subset:  IM    
Affiliation:
Department of Experimental Medicine, University of Erlangen-Nürnberg, Glückstr. 6, 91054 Erlangen, Germany. epoeschl@molmed.uni-erlangen.de
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MeSH Terms
Descriptor/Qualifier:
Aged
Aged, 80 and over
Aggrecans
Aging / genetics,  metabolism
Amino Acid Sequence
Cartilage, Articular / metabolism*
Chondrocytes / metabolism
CpG Islands
DNA Methylation*
Down-Regulation / genetics*
Extracellular Matrix Proteins / biosynthesis,  genetics*
Humans
Lectins, C-Type
Middle Aged
Molecular Sequence Data
Osteoarthritis / genetics*,  metabolism
Promoter Regions, Genetic / genetics
Proteoglycans / biosynthesis,  genetics*
Tumor Cells, Cultured
Chemical
Reg. No./Substance:
0/Aggrecans; 0/Extracellular Matrix Proteins; 0/Lectins, C-Type; 0/Proteoglycans

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